Project Summary/Abstract Cholera is an ancient disease that has shown a remarkable ability to persist and spread in the modern world. In WHO data for 2016, 132,121 cholera cases and 2420 deaths were reported from 38 countries. However, taking into account likely underreporting, the global disease burden has been estimated to be in the range of 1.3 to 4.0 million cholera cases and 21,000-143,000 deaths per year. Cholera is frequently a disease of poverty, striking in areas with humanitarian emergencies and crumbling public health infrastructure: most recently, this has been highlighted by the massive epidemic in Yemen, with over a million cases reported to date. Given the intransigence of such problems, and ongoing issues with climate change, urbanization, and population growth, cholera is likely to remain a recurring global threat to public health. While the Indian subcontinent is the ancestral home of cholera, and epidemics may occur in crisis situations such as currently seen in Yemen, over the past two decades sub-Saharan Africa has emerged as the primary locus of the global cholera disease burden. Within Africa, two major regional inland ?hotspots? of cholera activity have been identified: one in the Lake Chad region, and the other in the Great Lakes region, centered on Goma in the DRC. The WHO Global Task Force for Cholera Control has recently developed a ?global roadmap? leading toward cholera eradication, based on three strategic axes: the second of these axes is ?Prevention of disease reoccurrence by targeting multi-sectorial interventions in cholera hotspots.? Within this roadmap, they have also placed a strong focus on the need for country-level data, with targeting of interventions directed by an understanding of local circumstances and transmission patterns. Goma, with a population of over 1 million (including substantial refugee populations), is on the northern shore of Lake Kivu, bordering Rwanda; the city has had recurrent, annual cholera epidemics for at least the past decade, with phylodynamic analysis demonstrating the persistence of a ?Great Lakes? clade of V. cholerae O1 in the region. We are proposing a targeted, multi-sectorial analysis of cholera transmission in Goma, utilizing robust epidemiologic and phylodynamic techniques, with two major goals: 1) to further expand our understanding of how this ancient pathogen evolves and adapts to new geographic areas and new populations; and 2) to provide data for development of a practical, scientifically-informed plan for cholera control in this regional cholera hotspot, building on recommendations of the WHO Global Task Force. Specific Aims to accomplish these objectives: ? Specific Aim 1: Studies of cholera transmission and infection within households of suspected cholera cases in Goma; ? Specific Aim 2: Identification and assessment of aquatic environmental sources/reservoirs for cholera; and ? Specific Aim 3. Phylodynamic analysis of clinical and environmental V. cholerae O1 strains.